Comparison between serum theophylline levels after rectal and intravenous administration of aminophylline to preterm neonates At KNH Newborn Unit

Abstract

Background: Aminophylline IV formulation has traditionally been administered rectallv at the Kenyatta National Hospital Newborn Unit (KNH- NBU) to prevent and treat apnoea of prematurity (primary apnoea). Apnoea of prematurity (AOR) premature neonates especially those with a gestational age of 32 weeks and below. Previous studies on rectal aminophylline administration as enema or suppositories in preterm neonates recommended rectal route as a good alternative to oral or intravenous routes. I his study was conducted to compare serum theophylline levels after intravenous and rectal administration of the aminophvline IV formulation to preterm neonates at the KNII- NBU. Objective: To compare serum theophylline levels after IV aminophvline infusion and rectal administration of the IV aminophvline formulation to preterm neonates at the KNH- NBl Methods: Neonates with gestational age of 32 weeks and below were randomlv assigned to receive IV or rectal aminophylline. Eligibility criteria included stable inborn preterm neonates ol gestational age 32 weeks and below without sepsis, risk of sepsis or significant congenital anomalies. Consent was also obtained from the parent or guardian before a neonate was recruited into the study. Neonates who were on drugs that could interfere with theophylline metabolism were excluded. Aminophylline was administered at a loading dose of 5 mgs/kg body weight followed by 2 mgs /kg bodyweight per dose administered every 12hours in both arms of the study. Two mis (2) of blood were drawn at peak (Munir alter loading dose) and at steady stale, 72hours after initiation of aminophvline administration and 3 hours alter the 7lh aminophylline close for analysis of serum theophvlline levels. Serum theophylline levels were analysed using AxSYM Immunoassay .Analyser and I heophyllinc Reagent Kit (Abbot Laboratories). Baseline heart rates were recorded at admission and twice daily during the 72 hour period of follow up. Results: There were 61 neonates in each arm of the study. There was no significant difference in median birth weights between the two arms of the stud). The IV arm had a median birth weight of 1 25()g (range 6OO-1600) compared to 13()()g (range 800 -1600) in the rectal arm (p- 0.634). The IV arm had a median gestational age of 20\vccks (rangc26-32) compared to 30 weeks (range 26 -32) in the rectal arm.This difference in median gestational a^cs were not significant (p=0.334). Rectal arm had significant lower peak theophvlline ,cvcls (range 0.4-14.76) compared to 6.82 pg/ml (range 0.68-18.05) in the IV arm

(p=0.0004). The median steady state trough levels was still significantly lower at 6.6lpg/ml (range 0.41-16.46) in the rectal arm compared to 10.48 pg/ml (range 2.25-40) in the IV arm (p= 0.0001). Neonates in the rectal arm were two times more likely to attain sub therapeutic theophylline peak levels compared to the IV arm |()R 2.36(95%CI 1.06-5.27) p 0.021. Neonates in the IV arm were five times more likely to have toxicity at steady state trough levels |()R5.06 (95%C’I 1.2I-24.29).p=0.01 j and less likely to have sub therapeutic levels though this difference was not significant) OR 0.63 (95%CI 0.24-1.62). p- 0.201. Tachycardia was more evident after 72 hours (steady state). Neonates in the IV arm were two times more likely to have tachycardia at 72 hours compared to the rectal arm. a difference that was significant |RR 1.85 (95%CI 1.36-2.51). I* 0.0011. Conclusion Serum theophylline levels were sub therapeutic in most neonates one hour (peak levels) after rectal administration of IV aminophylline formulation. At steady state, rectal arm had more neonates with sub therapeutic levels while Intravenous arm had more neonates with toxic levels. Tachycardia was more prevalent after IV aminophylline infusion. The number of neonates with therapeutic serum theophylline levels at steady slate was comparable in the two arms of the study, from this study result, further research is recommended to look at whether serum theophylline levels would improve to be within therapeutic range in most neonates at peak and steady state if higher doses of IV aminophylline formulation are administered reclally or aminophylline loading doses are infused followed by maintenance doses rectal I y at the same doses and schedule used in this study.